Behavioral disinhibition such as increased impulsivity and aggression is typically observed in inebriated humans and alcoholics. Moreover, trait behavioral disinhibition strong correlates with alcohol addiction and abuse, suggesting that disinhibition and alcohol addiction have overlapping genetic or neural components. However, the neurobiological basis corroborating this notion is poorly understood. We found that Drosophila males exhibit disinhibited inter-male courtship, a type of cognitive behavioral disinhibition, with recurring ethanol treatment and dopamine neuronal activity is crucial for this phenomenon. Furthermore, the flies lacking dopamine transporter (DAT) display disinhibited motor behavior under the simultaneous influence of ethanol and social stress. These findings are novel and provide a unique system to unravel the neural and cellular mechanisms underlying ethanol-induced disinhibition. By employing powerful genetic resources available in Drosophila, the proposed research is directed at elucidating the mechanisms by which dopamine mediates ethanol-induced disinhibition. To achieve the goal, we will clarify the neural substrates and specific receptors mediating dopamine's functions in cognitive and motor disinhibition. The neuroanatomically simple and genetically amenable Drosophila offers tremendous advantages for this task. Numerous studies reveal striking similarities of various ethanol effects and the molecules mediating those effects in Drosophila and mammals. Notably, behavioral disinhibition is also observed in dopamine-related disorders such as attention deficit hyperactivity disorder, schizophrenia, Parkinson's disease, and substance abuse and addiction. Knowledge obtained in the proposed research will advance our understanding of behavioral disinhibition induced not only by ethanol but also by other addictive substances, genetic and social factors. PUBLIC HEALTH RELEVANCE: Behavioral disinhibition is typically associated with inebriated humans and alcoholics; however, its underlying mechanism is poorly understood. The proposed research is aimed at elucidating the neural and cellular mechanisms underlying ethanol-induced motor and courtship disinhibition.